Kirman C R, Hughes B, Becker R A, Hays S M
Summit Toxicology, Orange Village, OH 44022, USA.
The Dow Chemical Company, Midland, MI 48674, USA.
Regul Toxicol Pharmacol. 2016 Apr;76:137-51. doi: 10.1016/j.yrtph.2016.01.020. Epub 2016 Feb 3.
Diethanolamine (DEA) has been found to produce liver and kidney tumors in mice following lifetime dermal exposures. Data regarding the mode of action by which DEA produces these tumors were used to support a dose-response assessment that resulted in a no-significant-risk-level (NSRL) for dermal exposures to DEA. DEA and its metabolites are structural analogs to endogenous agents important to choline homeostasis. Sufficient information is available to support an epigenetic MOA involving the perturbation of choline homeostasis and hepatic methylation reactions in the formation of mouse liver tumors. This MOA may also apply to mouse kidney tumors, but direct measurements for key events in kidney are lacking. For both tumor types, dose-response data were pooled across four cancer bioassays conducted for DEA and DEA-containing condensates in order to provide a more robust characterization of the dose-response relationships. Doses were expressed in terms of dermally absorbed dose so that the dose-dependency and species differences in the dermal absorption of DEA were addressed. The resulting NSRL value of 3400 ug/day for dermal exposures to DEA is considered to be protective of human health for both tumor endpoints.
已发现二乙醇胺（DEA）在小鼠终生经皮暴露后会引发肝脏和肾脏肿瘤。关于DEA引发这些肿瘤的作用方式的数据被用于支持剂量反应评估，该评估得出了经皮暴露于DEA的无显著风险水平（NSRL）。DEA及其代谢物是对胆碱稳态至关重要的内源性物质的结构类似物。有足够的信息支持一种表观遗传作用机制，该机制涉及在小鼠肝脏肿瘤形成过程中胆碱稳态和肝脏甲基化反应的扰动。这种作用机制可能也适用于小鼠肾脏肿瘤，但缺乏对肾脏关键事件的直接测量。对于这两种肿瘤类型，为DEA和含DEA的缩合物进行的四项癌症生物测定中的剂量反应数据被汇总，以便更有力地描述剂量反应关系。剂量以经皮吸收剂量表示，从而解决了DEA经皮吸收中的剂量依赖性和物种差异问题。经皮暴露于DEA的最终NSRL值为3400微克/天，被认为对两种肿瘤终点都能保护人类健康。
